Postnatal development of female sheep pineal gland under natural inhibitory photoperiods: an immunocytochemical and physiological (melatonin concentration) study

The purpose of this study was to determine structural and immunocytochemical changes taking place during the day and at night in developing sheep pineal gland under natural non-stimulatory photoperiods (summer solstice). Additionally, the diurnal cycle of plasma melatonin levels was charted and differences between diurnal and nocturnal pineal melatonin concentrations were analyzed. 36 ewes of three different ages were examined: infants (1-6 months old), pubertal and early fertile age (9-24 months old) and adults (36-60 months old). Plasma and pineal gland melatonin levels were higher in pubertal sheep than in infants or adults. Pubertal sheep pineal glands were also heavier, contained a larger number of pinealocytes and interstitial cells and displayed more evident innervation and vascularisation than infants or adults. There was no difference in the number of pinealocytes and interstitial cells between animals killed during daylight or at night. Gland weight, pinealocyte nuclear profile areas and plasma melatonin concentrations were all significantly higher at night than during the day.     

Reproductive phase depedent circadian variation in the pineal biochemical constituents of Indian palm squirrel, Funambulus pennanti

In mammals, pineal gland is intimately concerned with the co-ordination of rhythm physiology. Biochemical characteristics of pineal gland in man and other mammals may provide strong, yet sometimes elusive support for the belief in functional individuality and probable importance of this tiny gland. In seasonal breeding animals, pineal gland function is very much dependent on the reproductive status. Therefore, the aim of this experiment is to note the circadian rhythmicity of different biochemical constituents of pineal gland during active and inactive phases of reproductive cycle of a seasonally breeding rodent, F. pennanti. In the present study, pineal biochemical constituents i.e. protein and cholesterol showed higher values during daytime (1400 h). The plasma melatonin level presented two peaks during active (April; at 1800 h and 0200 h) and inactive (December; at 1400 h and 0200 h) phases of reproductive cycle. The pineal protein, cholesterol and plasma melatonin values in term of basal and peak levels were higher during the reproductive inactive/pineal active phase. Therefore, pineal--also known to have antigonadotropic properties and cholesterol which appears conjugated with pineal serotonin, presented circadian rhythmicity along with the plasma level of melatonin. This rhythmicity noted in present study was dependent on the reproductive and pineal activity status, and might be regulated by the sex steroid receptor present on the pineal gland.     

Day-night changes in plasma melatonin levels,synaptophysin expression and ultrastructural properties of pinealocytes in developing female sheep under natural long and short photoperiods

The aim of the present study was to analyze the 24-h rhythm in plasma melatonin concentration and the day-night differences in synaptophysin expresion and ultrastructural characteristics of the pinealocytes in developing female sheep. Ewes of three different ages were examined: infantile (1-6 months old), pubertal and early fertile age (9-24 months old) and adult (36-60 months old). Experiments were conducted under natural non-stimulatory (long) and stimulatory (short) photoperiods. The obtained results were similar for both analyzed photoperiods. Plasma melatonin concentration, measured in samples obtained every 4 h, showed a similar pattern in the three age groups, with peak values at 02:00 h and troughs at 14:00 h. Mean value of plasma melatonin levels in 9-24 month-old sheep was significantly greater than that in younger or older sheep. The weight of pineal glands obtained at night (02:00 h) was significantly higher than in daylight (14:00 h). Pubertal and early fertile sheep had the largest pineal glands. The pineal volume, and the total number of pinealocytes per gland of 9-24 months-old sheep differed significantly from that of younger or older sheep. The pineal volume, and the mean volume of pinealocytes was significantly greater in animals killed at night. Number of pinealocytes did not vary between animals killed during daylight or at night. The mean volumen of pinealocytes did not show statistical differences between the age groups. In quantitative ultrastructural analysis of pinealocyte cells, the relative volume of mitochondria, rough endoplasmic reticulum and Golgi complexes was significantly greater in 9-24 month-old sheep and in animals killed at night. The relative volume of lipid droplets was highest in older sheep. Collectively, the data support the existence of developmental changes in pinealocyte morphology and quantity, partially in coincidence with a higher melatonin secretion rate.     

The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland--a tale of conflict and resolution

A theory is presented that explains the evolution of the pinealocyte from the common ancestral photoreceptor of both the pinealocyte and retinal photoreceptor. Central to the hypothesis is the previously unrecognized conflict between the two chemistries that define these cells-melatonin synthesis and retinoid recycling. At the core of the conflict is the formation of adducts composed of two molecules of retinaldehyde and one molecule of serotonin, analogous to formation in the retina of the toxic bis-retinyl ethanolamine (A2E). The hypothesis argues that early in chordate evolution, at a point before the genes required for melatonin synthesis were acquired, retinaldehyde--which is essential for photon capture--was depleted by reacting with naturally occurring arylalkylamines (tyramine, serotonin, tryptamine, phenylethylamine) and xenobiotic arylalkylamines. This generated toxic bis-retinyl arylalkylamines (A2AAs). The acquisition of arylalkylamine N-acetyltransferase (AANAT) prevented this by N-acetylating the arylalkylamines. Hydroxyindole-O-methyltransferase enhanced detoxification in the primitive photoreceptor by increasing the lipid solubility of serotonin and bis-retinyl serotonin. After the serotonin --> melatonin pathway was established, the next step leading toward the pinealocyte was the evolution of a daily rhythm in melatonin and the capacity to recognize it as a signal of darkness. The shift in melatonin from metabolic garbage to information developed a pressure to improve the reliability of the melatonin signal, which in turn led to higher levels of serotonin in the photodetector. This generated the conflict between serotonin and retinaldehyde, which was resolved by the cellular segregation of the two chemistries. The result, in primates, is a pineal gland that does not detect light and a retinal photodetector that does not make melatonin. High levels of AANAT in the latter tissue might serve the same function AANAT had when first acquired- prevention of A2AA formation.     

Daily cycles in plasma and ocular melatonin in demand-fed sea bass, Dicentrarchus labrax L.

Melatonin is regarded as an internal zeitgeber, involved in the synchronization to light of the daily and seasonal rhythms of vertebrates. To date, plasma and ocular melatonin in fish have been extensively surveyed almost solely in freshwater species – with the exception of some migrating species of salmonids. In the present paper, melatonin levels of a marine species (sea bass, Dicentrarchus labrax L) were examined. In addition, the daily rhythms of the demand-feeding activity of sea bass, a fish species characterized by a dual phasing capacity (i.e. the ability to switch between diurnal and nocturnal behaviour), were investigated before sampling. Sea bass, distributed in 12 groups of four fish and kept under constant water temperature and salinity, were exposed to a 12 h light:12 h dark cycle (200:0 lx, lights on at 0800 hours). After 4 weeks recording, the animals were killed at 0900, 1200, 1400, 1600, 1900, 2100, 2400, 0200, 0400, 0700 and 0900 hours. Actograms of demand-feeding records revealed a nocturnal feeding behaviour, with some cases of spontaneous inversions in phasing. Melatonin levels in plasma peaked in the middle of the dark phase, dropping after lights on. Melatonin in the eye, on the contrary, exhibited an inverse profile, with high levels during daytime and low levels at night. These results suggest that melatonin in the plasma and the eye may act independently on the flexible circadian system of sea bass. Accepted: 30 January 1997     

Age-related morphometric changes in the pineal gland. A comparative study between C57BL/6J and CBA mice

Relatively little is known about the effects of melatonin on the aging of the pineal, the organ which is the main place for synthesis of this hormone. Using simple morphometric methods, some parameters of the pineal gland, such as total volume, number of pinealocytes and pinealocyte volume were estimated in two mice strains: normal CBA and melatonin-deficient C57BL/6J. Two age groups, 6 weeks and 10 months, were studied in order to evaluate possible differential age-related changes between both strains. Pineals of both strains have similar morphometric and morphological features at 6 weeks of age. This suggests that pineal development, which has already concluded at 6 weeks of age, is not affected by the absence of melatonin synthesis in the pinealocytes. Later on, CBA pineal showed an increase in size caused by cellular hypertrophy. In contrast, the C57BL/6J pineal volume decreased by loss of pinealocytes in the same period of time. Semithin sections analysed by light microscopy did not show that this cell death was evident in the C57BL/6J strain at any of the ages studied. Thus, a gradual loss of pinealocytes could be hypothesised in these pineals. These results suggest that pineal melatonin could have a role in the maintenance of pinealocyte viability and the increase of pineal size which takes place after development. The abnormal pattern observed in the C57BL/6J pineal should be taken into account in future studies on this gland.     

The anatomy and innervation of the mammalian pineal gland

The parenchymal cells of the mammalian pineal gland are the hormone-producing pinealocytes and the interstitial cells. In addition, perivascular phagocytes are present. The phagocytes share antigenic properties with microglial and antigen-presenting cells. In certain species, the pineal gland also contains neurons and/or neuron-like peptidergic cells. The peptidergic cells might influence the pinealocyte by a paracrine secretion of the peptide. Nerve fibers innervating the mammalian pineal gland originate from perikarya located in the sympathetic superior cervical ganglion and the parasympathetic sphenopalatine and otic ganglia. The sympathetic nerve fibers contain norepinephrine and neuropeptide Y as neurotransmitters. The parasympathetic nerve fibers contain vasoactive intestinal peptide and peptide histidine isoleucine. Recently, neurons in the trigeminal ganglion, containing substance P, calcitonin gene-related peptide, and pituitary adenylate cyclase-activating peptide, have been shown to project to the mammalian pineal gland. Finally, nerve fibers originating from perikarya located in the brain containing, for example, GABA, orexin, serotonin, histamine, oxytocin, and vasopressin innervate the pineal gland directly via the pineal stalk. Biochemical studies have demonstrated numerous receptors on the pinealocyte cell membrane, which are able to bind the neurotransmitters located in the pinealopetal nerve fibers. These findings indicate that the mammalian pinealocyte can be influenced by a plethora of neurotransmitters.     

Simultaneous determination of N-acetyltransferase activity, hydroxyindole-O-methyl-transferase activity, and melatonin content in the pineal gland of the Syrian hamster

The activities of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) and the melatonin content were measured in Syrian hamster pineal glands at 2-hr intervals over a period of 24 hr. NAT and HIOMT are the two enzymes which catalyze the formation of melatonin from serotonin. The use of micromethods for determination of the enzyme activities allowed concurrent measurement of NAT and melatonin or HIOMT and melatonin in the same gland. HIOMT activity showed no significant diurnal rhythm whereas NAT activity and melatonin content exhibited distinct peak values late in the dark phase as described previously. Despite an apparent parallelism between the NAT activity rhythm and melatonin content, no correlation exists between these parameters in single pineal glands.     

Circadian Rhythms of Melatonin and Sex Steroids in a Nocturnal Bird, Indian Spotted Owlet Athene brama During Reproductively Active and Inactive Phases

The epiphyseal neurohormone melatonin (MEL) exhibits circadian cyclicity, as noted extensively in diurnal vertebrates although very little information is available regarding nocturnal species. We have studied the MEL rhythmicity with 24-hour periodicity in a tropical nocturnal bird, Indian spotted owlet Athene brama, which possesses a well-developed pineal organ. We performed our study during two crucial reproductive phases (active and inactive), when the pineal gland activity in owlet exists in inverse states, i.e., inactive and active respectively. Independent of sex, the circadian rhythm of plasma MEL in owlets showed a two-peak cyclicity with a smaller peak at around 1400 h and the higher one at about 0200 h, while the lowest value was found at 1000 h. The night (0200 h) peak activity of plasma MEL in owlet has a resemblance with the earlier findings in diurnal birds and strongly suggests that independent of species habit the peak activity of MEL is invariably dark dependent. However, the daytime peak of MEL may be due to the daytime hiding nature of this nocturnal bird. Interestingly, it was also noted that the hours of peak activity of MEL (1400 and 0200 h) were the same during both of the reproductive phases, though the environmental day length was longer and ambient temperature was higher during the reproductively inactive phase. During daytime these birds hide in a dark burrow where, in general, the intensities of light and temperature are less, and the amplitude of variations of these factors is not prominent. Hence, the seasonal variations in these oscillatory components may not have affected the entrainment of the owlet pineal oscillator, which regulates the daily MEL rhythm in a similar pattern during both the studied phases. On the other hand, a single circadian peak (around 1000 h) circadian cyclicity of gonadal steroids (i.e., testosterone in the male and estradiol and progesterone in the female) showed an inverse relationship with plasma MEL. Possibly, MEL regulates the daily steroidogenic status in owlets by an inhibitory influence.     

Circadian Rhythms of Melatonin and Sex Steroids in a Nocturnal Bird,Indian Spotted Owlet Athene brama During Reproductively Active and Inactive Phases

The epiphyseal neurohormone melatonin (MEL) exhibits circadian cyclicity, as noted extensively in diurnal vertebrates although very little information is available regarding nocturnal species. We have studied the MEL rhythmicity with 24-hour periodicity in a tropical nocturnal bird, Indian spotted owlet Athene brama, which possesses a well-developed pineal organ. We performed our study during two crucial reproductive phases (active and inactive), when the pineal gland activity in owlet exists in inverse states, i.e., inactive and active respectively. Independent of sex, the circadian rhythm of plasma MEL in owlets showed a two-peak cyclicity with a smaller peak at around 1400 h and the higher one at about 0200 h, while the lowest value was found at 1000 h. The night (0200 h) peak activity of plasma MEL in owlet has a resemblance with the earlier findings in diurnal birds and strongly suggests that independent of species habit the peak activity of MEL is invariably dark dependent. However, the daytime peak of MEL may be due to the daytime hiding nature of this nocturnal bird. Interestingly, it was also noted that the hours of peak activity of MEL (1400 and 0200 h) were the same during both of the reproductive phases, though the environmental day length was longer and ambient temperature was higher during the reproductively inactive phase. During daytime these birds hide in a dark burrow where, in general, the intensities of light and temperature are less, and the amplitude of variations of these factors is not prominent. Hence, the seasonal variations in these oscillatory components may not have affected the entrainment of the owlet pineal oscillator, which regulates the daily MEL rhythm in a similar pattern during both the studied phases. On the other hand, a single circadian peak (around 1000 h) circadian cyclicity of gonadal steroids (i.e., testosterone in the male and estradiol and progesterone in the female) showed an inverse relationship with plasma MEL. Possibly, MEL regulates the daily steroidogenic status in owlets by an inhibitory influence.     

Melatonin and locomotor activity in the fiddler crab Uca pugilator

The influence of melatonin on locomotor activity levels was measured in the fiddler crab Uca pugilator. First, activity in untreated, laboratory-acclimated crabs was measured over 48 hours in a 12L:12D photoperiod; this study showed a nocturnal increase in activity. In eyestalk-ablated crabs, overall activity was significantly reduced, and no significant activity pattern occurred. Next, crabs were injected with melatonin or saline (controls) at various times during the 12L:12D photoperiod (0900h, 1200h, and twice at 2100h; each trial was separated by 3-4 days) and monitored for 3 hr post-injection. Control crabs had low activity during early photophase, high at mid-photophase, increasing activity during the first scotophase trial, and decreasing activity during the second scotophase trial. Melatonin had no significant influence on activity when injected during the early-photophase activity trough or early-scotophase activity decline, but significantly increased activity when injected during the mid-photophase activity peak and early-scotophase activity incline. Next, crabs were injected during an early scotophase activity trough and monitored throughout the twelve-hour scotophase. Melatonin did not increase activity until the mid-scotophase activity increase, approximately 6 hours later, showing that the pharmacological dosage persisted in the crabs' systems and had later effects during the incline and peak of activity but not the trough. Eyestalk-ablated crabs were injected with melatonin or saline during early photo- and scotophase. Melatonin significantly increased activity in the photophase but not the scotophase trial, indicating that the responsiveness to melatonin continues following eyestalk removal, but the timing may not match that of intact crabs. Melatonin may be involved in the transmission of environmental timing information from the eyestalks to locomotor centers in U. pugilator.     

Ultrastructural studies on the mitochondria of the pinealocyte under conditions of persistent lighting--L24

Rat pinealocytes were found to contain mitochondria in three configurational states and they were calculated at 11.00 a.m. and 11.00 p.m. Their proportions were found to change in 24 hours. Analysis of these results indicated the existence of correlation between pinealocyte bioenergetics and melatonin biosynthesis and its lack in relation to serotonin. Cell groupings with mitochondria in the same configurational state were observed, which suggest the existence of functionally differentiated zones within the pineal gland.     

Aminergic innervation pattern of the rodent pineal gland: no apparent influence of time of day

Pineal melatonin synthetic activity shows distinct diurnal characteristics. The circadian regulation of melatonin synthesis is provided by noradrenaline-releasing sympathetic nerves. The pineal noradrenaline content shows a circadian rhythmicity tidally related to the changes in melatonin synthesis rate. To evaluate possible circadian changes of pineal noradrenergic fibre arrangement, the nerve distribution in rat and guinea pig pineal glands was visualized by means of glyoxylic acid-induced histofluorescence. Histochemical findings at 08.00 h and 24.00 h did not exhibit any differences: in both species a dense, mainly perivascularly located network of fluorescent fibres was encountered. As indicated by the simultaneous intraneural presence of green-bluish and yellow fluorophores these fibres most likely contain noradrenaline and serotonin. Obviously circadian melatonin synthesis changes are not paralleled by changes in the distribution pattern of pineal sympathetic nerve fibers. Like other sympathetic innervation-related morphological parameters, histofluorescence does not accurately reflect circadian biochemical changes in the pineal gland.     

Influence of melatonin and serotonin on the number of rat pineal “synaptic” ribbons and spherules in vitro

Summary Previous studies have shown that the synaptic ribbons (SR) and spherules (SS) of the mammalian pineal gland may respond differently under physiological and various experimental conditions. The aim of the present study was to gain insight into the mechanisms that may be responsible for the numerical changes of these organelles during a 24-h cycle. As the possibility exists that the structures are influenced by substances synthesized within the pinealocyte, rat pineal glands were cultured with and without added melatonin or serotonin, using an experimental protocol such that the addition of melatonin and serotonin mimicks the circadian changes of the respective substances within the pineal. The tissue was processed for electron microscopy and the numbers of SR and SS were counted in a unit area of pineal tissue. The results obtained indicate that melatonin added to the incubation medium increases the number of SR in the first half of the night; serotonin decreases SR numbers in the morning. SS numbers, by contrast, decrease following melatonin administration in the afternoon, and increase in the morning following serotonin administration. It thus appears that the numbers of SR and SS are influenced by melatonin and serotonin and that the two structures are regulated by differential, but nevertheless biochemically closely related mechanisms.Financial support of the Deutsche Forschungsgemeinschaft (Schwerpunktprogramm Neuroendokrinologie, Vo 135/8-4), the Polish Academy of Sciences (Research Program 10.4.04.6), and the Freunde der Universität Mainz e.V. is gratefully acknowledged.On leave from Department of Anatomy, University Medical School, Pécs, Hungary     

Does melatonin modulate beta-endorphin, corticosterone, and pain threshold?

Converging lines of evidence suggest that the pineal hormone, melatonin, may regulate changes in pain threshold by modulating fluctuations in opioid receptor expression and levels of beta-endorphin (beta-END). This study investigated whether the circadian oscillation in plasma melatonin is involved in the modulation of plasma beta-END immunoreactivity (beta-END-ir), and whether fluctuations in pain threshold measured using the hotplate test are contingent upon the fluctuation of these two hormones in Rattus Norvegicus. The role of melatonin was explored using light-induced functional pinealectomy (LFPX) to suppress nocturnal melatonin release. Pinealectomized rats were found to have significantly elevated levels of beta-END-ir compared to control animals at both photophase (398 +/- 89 pg/ml versus 180 +/- 23 pg/ml) and scotophase (373 +/- 45 pg/ml versus 203 +/- 20 pg/ml) test-periods, thus supporting the putative melatonin-opioid axis. Similarly, latency to pain threshold of LFPX rats was significantly longer when compared to control animals at photophase (7.3 +/- 1.4 sec versus 4.8 +/- 0.7 sec) and scotophase (6.3 +/- 0.7 sec versus 5.1 +/- 0.7 sec). Previous studies have produced conflicting data regarding the role of the pineal system in modulating levels of corticosterone (CORT). We observed a moderate, but non-significant, increase in the CORT concentration of LFPX rats during the photophase test period.     

Diurnal patterns of testosterone, dihydrotestosterone, estradiol, and cortisol in serum of rhesus males: Relationship to sexual behavior in aging males

This study was carried out to determine differences between old and young rhesus males in levels and diurnal patterns of testosterone, dihydrotestosterone, cortisol, and estradiol, and to determine correlations between these hormones and sexual behavior of the old males. Blood was drawn from old (n = 9) and young (n = 9) rhesus males over 5 consecutive days at 0900, 1300, and 2100 hr. The two groups of males did not differ in mean serum levels of testosterone, dihydrotestosterone, or estradiol at any time. Although the old and young did not differ in cortisol levels at 0900 and 1300 hr, the cortisol levels at 2100 hr were lower in the old males. Diurnal variations in testosterone, dihydrotestosterone, and cortisol were comparable in old and young males. Mean serum levels of estradiol were significantly higher at 0900 hr than at 1300 hr in the old males, whereas in the young males estradiol levels did not differ with time of day. There was a significant positive correlation between testosterone and yawning rate, and cortisol levels were correlated positively with rate of contacting, rate of mounting, and percentage of tests with erections. The decline in sexual performance of old rhesus males cannot be attributed to changes in the levels or diurnal patterns of testosterone, dihydrotestosterone, or estradiol, but lower cortisol levels in old males may contribute to the decline in sexual behavior.     

Evolution of The Vertebrate Pineal Gland: The Aanat Hypothesis

The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a ～24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N‐acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed.     

Ultrastructural and hormonal changes in the pineal-testicular axis following arecoline administration in rats

Arecoline is an alkaloid of betel nut of Areca catechu. Betel nut is chewed by millions of people in the world and it causes oral and hepatic cancers in human. It has therapeutic value for the treatment of Alzheimer and schizophrenia. Arecoline has immunosuppressive, mutagenic and genotoxic effects in laboratory animals. It also affects endocrine functions. The objective of this study was to investigate the effects of arecoline on pineal-testicular axis in rats. Since pineal activity is different between day and night, the current study is undertaken in both the photophase and scotophase. The findings were evaluated by ultrastructural and hormonal studies of pineal and testicular Leydig cells, with quantitations of fructose and sialic acid of sex accessories. Arecoline treatment (10 mg/kg body weight daily for 10 days) caused suppression of pineal activity at ultrastructural level by showing dilatation of the cisternae of the rough endoplasmic reticulum (RER), large autophagosome-like bodies with swollen mitochondrial cristae, numerous lysosomes, degenerated synaptic ribbons and reduced number of synaptic-like microvesicles. Moreover, pineal and serum N-acetylserotonin and melatonin levels were decreased with increased serotonin levels in both the gland and serum. In contrast, testicular Leydig cell activity was stimulated with abundance of smooth endoplasmic reticulum (SER), electron-dense core vesicles and vacuolated secretory vesicles, and increased testosterone level in the arecoline recipients. Consequently, the testosterone target, like prostate, was ultrastructurally stimulated with abundance of RER and accumulation of secretory vesicles. Fructose and sialic acid concentrations were also significantly increased respectively in the coagulating gland and seminal vesicle. These results were more significant in the scotophase than the photophase. The findings suggest that arecoline inhibits pineal activity, but stimulates testicular function (testosterone level) and its target organs presumably via muscarinic cholinergic receptor in rats.     

Evolution of Pineal Control of Endocrine Function in Lower Vertebrates

Pineal bodies, and other associated parietal structures, areremarkably varied among vertebrates These organs apparentlyassumed, in the primitive vertebrates, a principal role in integrationof photic information. The pineal photoreceptor cell seems tohave evolved into the secretory pinealocyte that is found inmost of the higher vertebrates. Along with the evolution ofthe photoreceptor element into the pinealocyte, there is a concomitantshift in the neural connection of the pineal organ. The pinealo-fugal,sensory innervation gives way to an autonomic, pinealo-petalmotor innervation. Thus, direct photosensitivity was supercededby indirect, optically-mediated control of the now secretorypineal gland. Even though pineal organs display such unusual plasticity anddiversity across groups, responsivenses to light remains a constantfeature. Photoperiod may modify the diurnallyrhythmic patternsof melatonin secretion across seasons and invoke appropriate"programs" which permit an animal to anticipate seasonal changes.Thus, melatonin may be a key molecule, attuned to photoperiodicity,which has been selected through evolution to effect adaptationto annual events.     

Evolution of the vertebrate pineal gland: the AANAT hypothesis

The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a approximately 24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed.